Intraperitoneal injection of BALB/cAn mice with pristane induces plasmacytomas after a long latency, which typically show c-myc-activating chromosome (6,15) or (12,15) translocations. Injection of the v-myc-carrying retrovirus J3 into pristane-primed animals accelerated plasmacytoma development and abrogated c-myc translocations, which provided the first direct evidence for the role of the translocation-activated c-myc in tumor development. Analysis of the J3 virus recovered after in vivo passage, termed J3Vl, showed reactivation of the deletion inactivated gag-v-raf present in J3. Further experiments analyzed recombinant retroviruses expressing different versions of v-myc and v-raf or combinations thereof for tumor induction in pristane-primed BALB/cAn mice. These experiments demonstrate the following: (1) v-myc is insufficient to transform B cells at any stage of differentiation. Viruses expressing MC29 v-myc (J5) efficiently cause monocytic tumors; presence of an MH2/MC29 hybrid v-myc (J5D, J3) showed no effect at all. (2) The combination of v-myc and v-raf in one virus (J2) resulted in lymphoid and monocytic tumors. J2 differs from J3Vl by the presence of 15 additional N-terminal amino acids in v-raf, which results in an increased transforming capacity. This suggests that attenuation of v-raf is essential for plasmacytoma acceleration. (3) Jl virus expressing an MSV 3611/MH2 hybrid raf(mil) induced no tumors, whereas MSV 3611 v-raf accelerated plasmacytomagenesis with a low incidence (20%). Preliminary characterization of these tumors provides evidence for deregulation of C-myc by insertional activation or chromosomal translocation, depending on the tumor isolate. Additionally, analysis of integrated virus shows alterations in the viral genome size. We also have biologically and molecularly cloned a variant of the MH2/MC29 hybrid v-mycexpressing virus J5D, J5D*, which was recovered from a lymphoblastic lymphoma in an NSF/N mouse injected as a newborn with the J5D virus. Unlike J5D, J5D* induced morphological transformation of fibro-blasts in culture and accelerates plasmacytomagenesis in BALB/cAn mice.